Coumarin 1,4-dihydropyridine hybrids: Synthesis, X-ray structure, cytotoxicity assay, and molecular dynamic simulation studies

This work aims to present the synthesis of coumarin 1,4-dihydropyridine (1,4-DHP) hybrid molecules with cytotoxic attributes through a triflic acid (trifluoromethane sulfonic acid, TfOH) catalyzed reaction involving 3-aminocoumarin, aromatic aldehydes and dimedone in refluxing ethanol. All the derivatives were obtained in good to excellent yields and fully characterized by IR, ¹H, and ¹³C NMR with HRMS, and single crystal XRD for selective molecules. The synthesized compounds were primarily assayed in vitro for cytotoxicity against the A549 cell line. The study of the binding interactions of the potent compound against eighteen different protein strands and MD simulation indicated the stable binding of the protein MTH1 to the ligand.